ABSTRACT Mounting evidence indicates that obesity, diabetes mellitus, and kidney stones are inter-connected diseases increasing in prevalence across the entire spectrum of American citizens. Linking these three disease states is intuitive, since food quantity, dietary factors, and body size all affect urinary composition and mineral excretion. Uric acid nephrolithiasis (UAN), with or without components of calcium oxalate (CO), is the second most common kidney stone type in the US and occurs only in acidic urine (pH < 5.8). Diabetics with overweight/obesity have a six-fold increased risk to develop UAN/COUAN because they are unable to properly add buffer (ammonium) to their urine. Alkali therapy, most commonly in the form of citrate salts, is the most widely used treatment for UAN/COUAN and has been reported in small series with limited follow-up to completely alkalinize urine to a normal range ? thus, ridding patients of their disease. Despite its reported simplicity, practical UAN/COUAN management with citrate salts is complicated by poor patient tolerance, early cessation, and questionable efficacy as only minimal long-term evidence for its use in this population exists. Furthermore, diabetics with renal disease may develop hyperkalemia on the required doses of potassium citrate, and effective blood pressure medications, such as angiotensin converting enzyme inhibitors or receptor blockers, can worsen the hyperkalemia risk. Finally, these therapies do not address the two important health epidemics that underlie and drive UAN/COUAN: obesity and diabetes. We propose an 18 month, feasibility pilot study entitled, ?Phentermine/tOpiramate to eND Obesity and Uric acid stones Trial? (POuND OUT). We will randomize thirty patients with obesity and UAN/COUAN to either an FDA-approved weight loss drug (phentermine plus topiramate-ER; Qsymia 15mg/92 mg; Vivus Inc.) or a pragmatic control group who remain on their standard medication regimen (citrate salts, allopurinol, diet, etc). Qsymia is not only expected to provide ~10% total body weight loss but also has a unique side effect of alkalinizing the urine (making it less acidic). This two-pronged approach is expected to reduce the burden of UAN/COUAN and obesity in these individuals while establishing a new class of medications for kidney stone prevention. Since no new drug therapies have been introduced in the area of stone disease in over 30 years, we feel the study objectives and research design are timely and may provide a feasible medication alternative to citrate salts for uric acid stone forming individuals with obesity.